Preparation and evaluation of fexofenadine microemulsion for intranasal delivery

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
International Journal of Pharmaceutics (Impact Factor: 3.65). 08/2010; 395(1-2):309-16. DOI: 10.1016/j.ijpharm.2010.05.041
Source: PubMed


To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine

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Available from: Chang Koo Shim, Oct 04, 2015
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    • "These adsorbent were used by some researcher to successfully develop solid SMEDDS to increase dissolution of lipophilic drug like Curcumin and Nitredipin (Wang et al. 2010). Till now fexofenadine microemulsion (Piao et al. 2010), solid dispersion (Jahan et al. 2011) and b-complexation (Pandya et al. 2011) were carried out to increase its bioavailability . Its poor aqueous solubility, substrate of P-glycoprotein and CYP 450 enzyme systems makes it suitable candidate for SEDDS. "
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    ABSTRACT: Fexofenadine, the active metabolite of terfenadine, a well known and effective H1 receptor antagonist, is administered by the oral route. The objective of present investigation was to develop and characterize a liquid self-emulsifying drug delivery system (SEDDS) and a solid SEDDS by using bioenhancer excipients like Tween 80 and Labrasol which are known for their inhibiting action on CYP450 and P-glycoprotein pump. Solubility of fexofenadine was determined in various vehicles, including oils, surfactants and co-solvents. Various evaluation parameters (emulsification study, particle size, poly-dispersibility index, % drug release, etc.) were carried out to find out optimized liquid SEDDS formulation. Optimized liquid formulations were converted in solid SEDDS by simple and convenient physical adsorption technique. Solid SEDDS was characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transport infra-red spectroscopy. The optimized liquid SEDDS formulation contained 29 % Captex 200P/Capmul MCM C8 EP as oil, 47 % Labrasol/Tween 80 as a surfactant and 24 % Ethanol as a co-solvent. The optimized liquid and solid SEDDS showed higher drug release than pure API powder. DSC and XRD results of solid SEDDS confirmed that the drug presented in the formulation was in an amorphous state. The prepared liquid SEDDS and solid SEDDS containing bio-enhancer excipients increased the in vitro dissolution rate of fexofenadine compared to pure drug and has potential to increase bioavailability by blocking Pgp efflux pump and CYP450 hepatic metabolism.
    Journal of Pharmaceutical Investigation 10/2013; 43(5). DOI:10.1007/s40005-013-0083-2
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    • "However, among these mediators, antihistamine remains the principal one, and plays a fundamental role in the genesis of allergic rhinitis. Therefore, antihistamines have been the main class of medications used for the treatment of allergic rhinitis over the past 60 years.2,3 "
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    ABSTRACT: Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In this work, novel FEX loaded water in oil microemulsion (w/o) was designed to improve bioavailability and compared with Fexofen(®) syrup in in vitro and in vivo studies. In addition, pharmacokinetic parameters in permeability studies were estimated by using WinNonLin software program. w/o microemulsion system was optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68 (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture; oil and cosurfactant was developed for oral drug delivery. w/o microemulsion systems were characterized by phase behavior, particle size, viscosity and solubilization capacity. In vitro studies were studied using Caco-2 cell monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in rabbits and compared to Fexofen(®) syrup. Fexofen(®) syrup and microemulsion were administered by oral gavage at 6 mg/kg of the same concentration. The experimental results indicated that microemulsion (HLB = 5.53) formed nanometer sized droplets (33.29 ± 1.76) and had good physical stability. This microemulsion increased the oral bioavailability of FEX which was highly water-soluble but fairly impermeable. The relative bioavailability of FEX microemulsion was about 376.76% compared with commercial syrup in rabbits. In vitro experiments were further employed for the enhanced effect of the microemulsion for FEX. These results suggest that novel w/o microemulsion plays an important role in enhancing oral bioavailability of low permeability drugs.
    International Journal of Nanomedicine 08/2011; 6:1631-40. DOI:10.2147/IJN.S22673 · 4.38 Impact Factor
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    ABSTRACT: Carbamazepine is widely preferred therapy for the treatment of epilepsy. However, oral therapy results in slower brain uptake and systemic side effects. Intranasal route can achieve faster brain uptake, but poor aqueous solubility of carbamazepine is the main obstacle for administration by nasal route. The purpose of this study was to prepare and evaluate intranasal oil in water microemulsion of carbamazepine to improve its solubility and enhance the brain uptake. Intranasal microemulsion of carbamazepine was prepared by water titration method using oleic acid as oil, Tween 80 as surfactant and Transcutol® as cosurfactant. Microemulsions were evaluated for various physical parameters including globule size, viscosity, pH and conductivity. Toxicity study of microemulsion was carried out by employing sheep nasal mucosa. The microemulsion was also evaluated by maximal electric shock, and the brain uptake study was done using HPLC method. The microemulsion was stable and transparent with average globule size of 21.03 nm and did not show any toxic symptoms. It showed reduction in the hind limb extension phase and faster recovery from seizures in comparison to oral microemulsion and nasal solution. Higher brain/plasma ratio was obtained with nasal microemulsion in comparison to ratio obtained after intraperitoneal injection of carbamazepine solution.
    Drug Delivery and Translational Research 06/2013; 3(3). DOI:10.1007/s13346-012-0126-7
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